CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia.
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
01 09 2023
01 09 2023
Historique:
received:
22
11
2022
revised:
31
03
2023
accepted:
12
06
2023
medline:
23
10
2023
pubmed:
16
6
2023
entrez:
16
6
2023
Statut:
ppublish
Résumé
Identifying mechanisms underlying relapse is a major clinical issue for effective cancer treatment. The emerging understanding of the importance of metastasis in hematologic malignancies suggests that it could also play a role in drug resistance and relapse in acute myeloid leukemia (AML). In a cohort of 1,273 AML patients, we uncovered that the multifunctional scavenger receptor CD36 was positively associated with extramedullary dissemination of leukemic blasts, increased risk of relapse after intensive chemotherapy, and reduced event-free and overall survival. CD36 was dispensable for lipid uptake but fostered blast migration through its binding with thrombospondin-1. CD36-expressing blasts, which were largely enriched after chemotherapy, exhibited a senescent-like phenotype while maintaining their migratory ability. In xenograft mouse models, CD36 inhibition reduced metastasis of blasts and prolonged survival of chemotherapy-treated mice. These results pave the way for the development of CD36 as an independent marker of poor prognosis in AML patients and a promising actionable target to improve the outcome of patients. CD36 promotes blast migration and extramedullary disease in acute myeloid leukemia and represents a critical target that can be exploited for clinical prognosis and patient treatment.
Identifiants
pubmed: 37327406
pii: 727330
doi: 10.1158/0008-5472.CAN-22-3682
pmc: PMC10472106
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2824-2838Informations de copyright
©2023 The Authors; Published by the American Association for Cancer Research.
Références
J Clin Invest. 1987 Apr;79(4):1054-61
pubmed: 2435757
Cell Stem Cell. 2016 Jul 7;19(1):23-37
pubmed: 27374788
Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4356-64
pubmed: 17003426
J Hematol Oncol. 2022 May 13;15(1):60
pubmed: 35562747
Exp Cell Res. 2022 Jun 1;415(1):113112
pubmed: 35346671
Nature. 2018 Oct;562(7728):526-531
pubmed: 30333627
Leuk Res. 2004 Oct;28(10):1007-11
pubmed: 15289011
Cell Death Dis. 2020 Apr 23;11(4):267
pubmed: 32327627
Oncotarget. 2017 Apr 26;8(44):75881-75892
pubmed: 29100277
Arterioscler Thromb Vasc Biol. 2013 Jul;33(7):1655-62
pubmed: 23640500
Cancer Discov. 2021 Jun;11(6):1542-1561
pubmed: 33500244
Leukemia. 2004 Jan;18(1):57-62
pubmed: 14586480
Ann N Y Acad Sci. 2001 Dec;947:350-5
pubmed: 11795289
Oncogene. 2021 Nov;40(47):6494-6512
pubmed: 34611309
J Transl Med. 2019 Oct 26;17(1):352
pubmed: 31655604
Cell Rep. 2019 Dec 10;29(11):3405-3420.e5
pubmed: 31825825
Cancer Cell. 2016 Jul 11;30(1):43-58
pubmed: 27344946
Blood Cancer Discov. 2020 Sep;1(2):198-213
pubmed: 32944714
Cancer Cell. 2018 Sep 10;34(3):483-498.e5
pubmed: 30205048
Cancer Discov. 2020 Apr;10(4):506-525
pubmed: 32014868
Blood Cancer J. 2017 Nov 29;7(12):635
pubmed: 29184070
Blood. 2010 Jan 21;115(3):453-74
pubmed: 19880497
Cancer Discov. 2017 Jul;7(7):716-735
pubmed: 28416471
J Biol Chem. 1993 Jun 5;268(16):11811-6
pubmed: 7685021
Haematologica. 2009 Jan;94(1):131-4
pubmed: 18838472
Sci Signal. 2009 May 26;2(72):re3
pubmed: 19471024
Sci Rep. 2016 Dec 06;6:38310
pubmed: 27922115
Cancer Res. 2011 Dec 15;71(24):7649-58
pubmed: 22037878
Leuk Res. 2005 Oct;29(10):1109-16
pubmed: 16095690
Int J Biochem Cell Biol. 2013 Sep;45(9):2087-96
pubmed: 23871936
EMBO Rep. 2018 Jun;19(6):
pubmed: 29777051
Semin Thromb Hemost. 2004 Feb;30(1):127-36
pubmed: 15034804
N Engl J Med. 2013 May 30;368(22):2059-74
pubmed: 23634996
J Clin Oncol. 1997 Feb;15(2):466-75
pubmed: 9053467
Cell Metab. 2020 Sep 1;32(3):391-403.e6
pubmed: 32763164
Nat Commun. 2020 Jan 23;11(1):454
pubmed: 31974393
Blood. 2010 Jul 22;116(3):354-65
pubmed: 20385793
Eur J Haematol. 2013 Apr;90(4):273-8
pubmed: 23470093
Nat Cancer. 2021 Nov;2(11):1204-1223
pubmed: 35122057
J Clin Oncol. 2016 Oct 10;34(29):3544-3553
pubmed: 27573652
Nature. 2017 Jan 5;541(7635):41-45
pubmed: 27974793
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
Nat Rev Cancer. 2021 Jul;21(7):461-475
pubmed: 33953370
Blood. 2013 Feb 28;121(9):1633-43
pubmed: 23297133
Nature. 2023 Jan;613(7942):169-178
pubmed: 36544018
Blood. 2017 Mar 9;129(10):1320-1332
pubmed: 28049638
Blood. 2021 Feb 4;137(5):678-689
pubmed: 33538796
J Thromb Haemost. 2011 Sep;9(9):1835-46
pubmed: 21696539
Cancer Discov. 2021 Feb;11(2):500-519
pubmed: 33028621
Oncogene. 2018 Apr;37(17):2285-2301
pubmed: 29398710